本文關鍵詞：炎性因子活化星形膠質細胞對T細胞調節(jié)機制研究　出處：《第三軍醫(yī)大學》2006年博士論文　論文類型：學位論文

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【摘要】： 緊密的血腦屏障(blood-brain barrier,BBB)和免疫抑制微環(huán)境的存在使中樞神經(jīng)系統(tǒng)(central nervous system, CNS)一直被認為是免疫特赦區(qū)。但在腦外傷、炎癥等情況下,白細胞可通過破壞的BBB進入腦內。大量研究顯示,CNS內存在特異性的T細胞免疫應答,在抗微生物感染、多發(fā)性硬化癥、自身免疫性腦炎以及腦血管病等多種疾病中發(fā)揮重要作用。然而,由于腦實質內缺乏淋巴管引流和對啟動免疫應答起重要作用的專職抗原提呈細胞(antigen-presenting cell,APC),初始T細胞被抗原活化的啟動過程可能主要在外周淋巴器官中完成,而活化的T細胞或致敏的T細胞穿過BBB后,被CNS內的APC再次激活,從而發(fā)揮免疫效應。此外,在CNS內的特殊微環(huán)境中,由于T細胞活化后存活期短、增殖能力弱以及接受再刺激時的快速凋亡,使得活化后T細胞的效應維持機制顯得尤為重要。目前,CNS內的膠質細胞如何參與T細胞免疫應答過程及其作用地位已成為神經(jīng)免疫領域倍受關注的問題之一。 星形膠質細胞(Astrocytes,Ast)作為大腦內最多的細胞群,發(fā)揮著維持大腦微環(huán)境穩(wěn)態(tài)的重要生理功能,而其神經(jīng)免疫功能往往被忽視,一般認為小膠質細胞才是腦內行使免疫呈遞和免疫調控功能的細胞。但是最近的研究證實,星形膠質細胞可以表達免疫膜分子,分泌炎性因子和釋放補體等,參與腦內炎性疾病的發(fā)生發(fā)展,從而逐漸受到神經(jīng)免疫學者的關注和重視。星形膠質細胞能夠維持大腦的免疫穩(wěn)態(tài),除通過血腦屏障中豐富的足突結構形成機械屏障以外,可能還存在有生物學屏障,如免疫抑制性分子的存在和分泌抑制性細胞介質發(fā)揮免疫保護效應。提示星形膠質細胞有可能成為CNS內免疫效應細胞,參與腦內炎性調控作用。研究證實,星形膠質細胞對內環(huán)境改變如炎性刺激、缺血、缺氧以及腦外傷等有高度敏感性,將出現(xiàn)反應性的改變,通常稱為“活化”或“膠質化”,即星形膠質細胞在炎性病變中的可塑性變化。已有研究報道證實星形膠質細胞在受到炎性介質的刺激后,血腦屏障的通透性增加,易于T細胞浸潤,參與疾病進程。在體通過EAE模型證實活化后的星形膠質細胞具有抗原處理、提呈功能,可以再次活化T淋巴細胞,加劇疾病的發(fā)展。因此,星形膠質細胞在CNS內T細胞活化后效應以及對T細胞功能的調控顯得極為重要,但這一過程中涉及到CNS內的細胞和T淋巴細胞作用的分子機制目前尚不確切。
[Abstract]:Tight blood-brain barrier (BBS) and blood-brain barrier. BBB) and immunosuppressive microenvironment make the central nervous system central nervous system (CNSs) have been considered as immune amnesty area, but in brain trauma. In cases such as inflammation, leukocytes can enter the brain through damaged BBB. A large number of studies have shown that there is a specific T cell immune response in anti-microbial infections, multiple sclerosis. Autoimmune encephalitis and cerebrovascular diseases play an important role. Because of the lack of lymphatic drainage in the brain parenchyma and the specialized antigen-presenting cell (APC) which plays an important role in initiating the immune response. The priming process of initial T cell activation by antigen may be mainly completed in peripheral lymphoid organs, while activated T cells or sensitized T cells pass through BBB and are reactivated by APC in CNS. In addition, in the special microenvironment of CNS, the survival time of T cells after activation is short, the ability of proliferation is weak, and the rapid apoptosis after re-stimulation. It is very important to maintain the effect of activated T cells. How glial cells in CNS participate in T cell immune response and its role has become one of the most concerned issues in the field of neuroimmunity. As the largest cell group in the brain, astrocytes play an important role in maintaining the homeostasis of microenvironment, but its neuroimmune function is often neglected. It is generally believed that microglia are the cells in the brain that perform immunological presentation and immunomodulation. However, recent studies have confirmed that astrocytes can express immune membrane molecules, secrete inflammatory factors and release complement, etc. Participate in the development of inflammatory diseases in the brain, and gradually attracted the attention of neuroimmunologists. Astrocytes can maintain the immune homeostasis of the brain. In addition to the mechanical barrier formed by the abundant podocyte structure in the blood-brain barrier, there may also be a biological barrier. For example, the existence of immunosuppressive molecules and secretion of inhibitory cell mediators play an immunoprotective effect. It is suggested that astrocytes may become immune effector cells in CNS and participate in the regulation of inflammation in brain. Astrocytes are highly sensitive to changes in the internal environment, such as inflammatory stimulation, ischemia, hypoxia, and brain trauma, and will present reactive changes, commonly known as "activation" or "glialization". That is the plasticity of astrocytes in inflammatory lesions. It has been reported that astrocytes stimulated by inflammatory mediators increase the permeability of blood-brain barrier and are easy to infiltrate T cells. Participate in the disease process. In vivo through the EAE model confirmed that activated astrocytes have antigen processing, presenting function, can reactivate T lymphocytes, aggravate the development of the disease. The effect of astrocytes on T cell activation and the regulation of T cell function in CNS are very important. However, the molecular mechanism involved in the action of cells and T lymphocytes in CNS is uncertain.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R392

【共引文獻】

相關期刊論文 前6條

1 熊加祥,白云,宋敏,許雪青,王艷艷,楊曉亞;星形膠質細胞抑制T細胞增殖及機制探討[J];第三軍醫(yī)大學學報;2005年20期

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3 李寶華;蔣正剛;徐林;李康;熊思東;;CVB3感染對星形膠質細胞表達agrin的影響及意義[J];復旦學報(醫(yī)學版);2007年05期

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本文編號：1364290